Architecture of autoinhibited and active BRAF-MEK1-14-3-3 complexes

Dr. Mike Eck and colleagues have published their tour de force structural study of BRAF in complex with MEK and 14-3-3 dimers. This work explains longstanding questions about the biochemical behavior of BRAF and provides a foundation for understanding BRAF activation by oncogenic mutations as well as pharmacologic inhibition. Please go to: to read the abstract and learn more. Congratulations to Mike and his scientific team!

Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.

In this featured publication, lead authors Zachary Reitman, MD, PhD and Brenton Paolella, PhD, and others with Mimi Bandopadhayay, MBBS, PhD and Rameen Beroukhim, MD, PhD use single cell sequencing technology to examine the cellular state of individual tumor cells. They find that PA cancer cells often look like astrocytes at the RNA level, but a few cells look like progenitor cells. Intriguingly, it is this smaller population of cells that may drive tumor growth more than the abundant astrocyte-like cells. There are also many immune cells, especially microglia. These findings will inform the design of therapies specific for the different cell types. Please click the link to go to the paper to learn more.

Management of pediatric low-grade glioma.

In this featured publication, investigators review recent results of treatments for pediatric low-grade gliomas, including standard chemotherapy, therapies targeting the mitogen-activated protein kinase (MAPK) pathway, and proton-beam radiation therapy.

Brainstem angiocentric gliomas with MYB-QKI rearrangements.

In this featured publication, Drs. Bandopadhyay and Ligon examine the potential for using the MYB-QKI rearrangement as a diagnostic marker in ambiguous or atypical low-grade glioma cases.

Characterizing genomic alterations in cancer by complementary functional associations

In this month’s featured publication, Drs. Hahn and Beroukhim and colleagues present REVEALER, a computational tool to investigate the functional consequences of the many mutations identified in tumor samples.  Distinguishing “driver” mutations that underlie oncogenic phenotypes from “passenger” mutations with no evident functional consequences is critical to the development of effective targeted therapies. This publication demonstrates the ability of REVEALER to identify both known and new associations of defined mutations with functional states correlated with oncogenesis.

Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma

In this month’s featured publication, Dr. Ligon and colleagues analyzed 134 diffuse intrinsic pontine glioma (DIPG) samples for their genetic make-up.  They determined that the DIPG tumors are associated with a particular mutation H3K27M, which is the initial driver of tumor formation, and that this mutation is maintained throughout the course of disease.  These findings confirm the use of needle biopsies for DIPG as the best method of sampling the tumor to find the driver, and that therapy should be focused on early systemic tumor control.

Clinical and treatment factors determining long-term outcomes for adult survivors of childhood low-grade glioma: A population-based study.

In this month’s Featured Publication, Dr. Kieran and colleagues studied the outcomes of adult survivors of pediatric low-grade glioma over a 27 year span.  They found that overall, patients showed excellent long-term survival, but this was somewhat decreased in patients who had received upfront radiotherapy.  The article suggests that these observations be considered when treatment option are being weighed for low-grade glioma patients.

MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism

In this month’s featured publication, researchers from the PLGA Program and their collaborators identify a new genetic driver of pediatric angiocentric glioma, called MYB-QKI.  The genetic driver of angiocentric gliomas was previously unknown.  MYB-QKI is an fusion protein that can drive tumor formation by several mechanisms, and its presence in a tumor sample provides an important diagnostic tool and an avenue for therapy in angiocentric glioma.

Myxopapillary ependymomas in children: imaging, treatment and outcomes

In this month’s featured publication, Drs. Ligon, Beroukhim, Kieran and colleagues published a study of the treatment and outcome of children with myxopapillary ependymomas (MPE), a rare spinal tumor.  They examined the diagnosis, imaging, treatment and clinical outcome of eighteen children over a period of 30 years, and found patients with MPE have an excellent overall clinical survival rate, and recommended that treatment strategies to minimize toxicity due to irradiation and chemotherapy approaches.

Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets.

In this month’s featured publication, Drs. Santagata, Ligon, and Beroukhim and colleagues published a study where they analyzed brain metastases for alterations in their genetic profiles.   In about half of the cases they found different genetic alterations in the brain metastases when compared with the primary tumor site.  This study showed that the genetically different brain metastases were not detected when a patient undergoes a primary tumor biopsy, suggesting that sequencing the primary tumor alone may miss substantial opportunities for targeted therapy.